DESCRIPTION Abstract The circuits in the brain that mediate our perception of reward, known collectively as the "reward system," couple pleasure with the essentials of life: food and reproduction. The reward system also lies at the root of some of the most tragic, harmful, and costly behaviors in our society. These include addiction to substances of abuse, obesity-related behavior, dangerous thrill seeking behavior, and aberrant sexual behavior. Research that I performed on altruistic behavior in honey bees has led me to a new insight about the reward system. Finding that the same neurochemical system that modulates selfish behavior in solitary insects modulates altruistic behavior in the highly social honey bee, I conclude that not only is the reward system vulnerable to "hijacking"- -coupling to stimuli with negative consequences-- over the course of a lifetime as mentioned above, but it also is vulnerable to hijacking in evolutionary time. I propose to use 'omic technologies (high-throughput sequencing, transcriptomics, epigenomics, proteomics, and metabolomics) to understand in molecular terms how to "flip" the reward system, from selfish to altruistic behavior. These analyses will be performed on a carefully selected set of closely related species of bees, some social (with altruistic behavior) and some solitary (without). The insights gained from this novel synthesis of systems biology, neuroscience, and evolutionary biology will transform our understanding of drug addiction and other diseases of the reward system and provide the foundation for new forms of therapeutic intervention. Public Health Relevance This project addresses the molecular basis of drug addiction and other diseases of the reward system, which are serious public health concerns. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES. COMMITTEE BUDGET RECOMMENDATIONS: The budget was recomme